This chapter talks about the author's goal to learn the latest molecular techniques that had been developed during the initial recombinant DNA era and to apply them to a clinically relevant problem. His project was undertaken at the beginning of the recombinant DNA era, and the potential applications of molecular methods to diagnostic microbiology and infectious diseases seemed limitless. Hopkins et al. continued to trace the evolution of antibiotic resistance and discovered that resistance and transmission of resistance markers evolve in very complex ways, demonstrating in a very contemporary way what Louis Pasteur said more than 100 years before the discovery of plasmids and transposons: "The bacteria will always have the last word." Molecular methods are very useful tools for solving epidemiological problems and for detecting and identifying both "old" and "new" pathogens. In addition to their utilities in solving infectious disease "mysteries," in some instances the data derived from these techniques have provided a foundation upon which to approach the study of microbial pathogenesis. This is well illustrated by current studies in the laboratory and in others to investigate the nature of the genes in Rochalimaea species encoding pathogenic determinants; these were spawned by molecular epidemiological studies to detect and characterize the infectious agents that cause bacillary angiomatosis and cat scratch disease. As much as this chapter concerns molecular epidemiology, it also reflects the author’s exposure to Stanley's approach to the pathogenesis of infectious diseases.